A pleiotropic response associated with resistance of breast cancer cells to antineoplastic drugs and hormonal agents.
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Biomedical subjects
Publications and source records attributed to R B Dixon.
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Thirty men recently treated for alcohol withdrawal were enrolled in a three-way crossover double-blind study with a balanced incomplete block design. Patients received single doses of three of the following: halazepam, 320 mg; halazepam, 160 mg; diazepam, 40 mg; diazepam, 20 mg; and placebo. The doses of the drugs were approximately equivalent in anxiolytic effect. Patients rated themselves at baseline, 30 min after, and 1, 2, 3, 4, 6, and 8 hr after drug on the following: euphoria, sedation, "drug-liking," "feeling the drug," and drug identification. By 30 min both diazepam groups reported increases in euphoria, sedation, and feeling and liking the drug; halazepam groups reported little subjective change at 30 min, and at 1 hr subjective effects did not differ from placebo on any scale. At 2 and 3 hr, both halazepam doses induced subjective effects on several scales, but peak effects were lower than peak effects of high diazepam doses. Unlike diazepam, the higher halazepam dose did not appear to induce greater effects than the lower dose. At peak, more of the diazepam group correctly identified the drug than those in the halazepam groups. More in the halazepam groups identified it as placebo than either diazepam group. To the degree that abuse potential is related to peak intensity and to time of onset of those subjective effects described as pleasant or likable, halazepam should have a lower potential for abuse than diazepam.
Five patients who had received corticosteroids for periods of years experienced steroid withdrawal symptoms when attempts were made to reduce or discontinue the drugs. Summarized herein are studies of hypothalmic-pituitary-adrenocortical (HPA) function in these five people during corticosteroid withdrawal. Analysis of these data and of data in previous reports discloses four subgroups of corticosteroid withdrawal syndrome: Type I, symptomatic and biochemical evidence of HPA suppression; type II, recrudescence of the disease for which the drug was originally described; type III, dependence upon corticosteroids, either physical or psychological, with demonstrably normal HPA function and no recrudescence of underlying disease; and type IV, biochemical evidence of HPA suppression without symptoms and without recurrence of underlying disease. Any combination of types I, II and III may exist. The major conclusions are these five. (1) Some syndromes that clinically suggest HPA suppression are not. (2) Some syndromes that resemble drug-dependence are not. (3) The rapid ACTH test is a clinically useful way to assess HPA function; this test should govern the rate of corticosteroid withdrawal in the absence of steroid-treatable disease. (4) If disease is present, the rate and degree of corticosteroid withdrawal are governed by the status of the disease. (5) Patients have an unpredictable tendency to abuse corticosteroids; physicians should guard against inattentively permitting long-term, unnecessary overdosage to continue.
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